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Background: The clinical efficacy of the third Military Medical University formula (TMMU formula) for fluid resuscitation stage was evaluated to improve the treatment level of adult patients with extensive burns during the shock stage. Methods: Retrospective analysis of the data of 55 patients undergoing fluid resuscitation according to the TMMU formula within six hours after burn injury. The following indicators were collected: (1) demographic and injury information; (2) fluid resuscitation information; (3) efficiency information, including cardiovascular function, liver function, renal function, coagulation function evaluation indicators, blood concentration, and average urine output index. Results: (1) In the first and second 24 hours after injury, the median fluid rehydration coefficient was 1.68 ml/kg·(%) TBSA and 1.15 ml/kg·(%) TBSA, the median ratio of crystal to colloid was 2.24 and 1.67, and the median urine output index was 0.75 ml/kg·h and 1.05 ml/kg·h, respectively. (2) The actual fluid volume during patient resuscitation is higher than the formula calculated volume, and this difference is more obvious in patients with burn area ≥80%. (3) In the second 24 hours, the value of the actual total fluid volume minus the formula total volume in the group with crystal to colloid ratio ≤2 was significantly lower than that in the ratio >2 group. (4) At 24 and 48 hours after injury, the cardiovascular function, liver function, renal function, and coagulation function were better than those before fluid resuscitation. Conclusions: Early application of the TMMU formula for fluid resuscitation in adult patients with extensive burns is safe and effective, but the actual input volume often exceeds the volume calculated by the formula, especially in the second 24 hours after burn injury and in patients with larger burn areas. Increasing the colloid input volume can help reduce the total amount of fluid used for resuscitation.
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The current study investigated the effects of sinapic acid on high-fat diet (HFD)-induced lipid metabolism and oxidative stress in male Syrian hamsters. Sinapic acid treatment significantly reduced body weight, epididymal fat, and perirenal fat mass in HFD hamsters. Sinapic acid also improved dyslipidemia levels (reducing the serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and increasing the high-density lipoprotein cholesterol) and increased T-AOC levels to mitigate oxidative stress injury. Moreover, sinapic acid intervention increased the activations of PPAR-γ, CPT-1, and CYP7A1 and decreased the activations of FAS, ACC1, SREBP1, SREBP2, and HMGCR in the livers of HFD hamsters. In addition, sinapic acid intervention also significantly inhibited the intestinal mRNA levels of Srebp2 and Npc1l1 in HFD hamsters. In conclusion, sinapic acid can significantly attenuate abnormal lipid metabolism in the development of HFD-induced obesity and reduce the level of oxidative stress to exert its anti-obesity effect. PRACTICAL APPLICATIONS: Obesity is the main cause of some chronic metabolic syndromes, such as dyslipidemia, nonalcoholic fatty liver disease, diabetes, and hyperuricemia. Searching for new, safe, and effective natural products in weight loss and fat reduction has become one of the hot research topics. As a natural source of simple phenolic acids, sinapic acid is present in fruits, vegetables, and grains and has been indicated to have anti-inflammatory, antioxidant, antihyperuricemic, lipid homeostasis regulation, and anticancer activities. However, the lipid metabolism- and oxidative stress-regulating activities of sinapic acid are not clear. Here, the current study investigated the lipid metabolism and oxidative stress regulating activities of sinapic acid in male Syrian hamsters fed a high-fat diet.
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Dieta Alta en Grasa , Dislipidemias , Cricetinae , Animales , Masculino , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos , Mesocricetus , Colesterol , Estrés Oxidativo , Obesidad , Dislipidemias/tratamiento farmacológico , Dislipidemias/etiologíaRESUMEN
BACKGROUND: Hands are one of the most common burn sites in children. Hypertrophic scar contractures in hands after wound healing result in further reductions in their range of motion (ROM), motility, and fine motor activities. Rehabilitation can improve the function of hands. But the optimal time of rehabilitation intervention is still unclear. Therefore, this study was designed to investigate the effects of early rehabilitation management of paediatric burnt hands and to compare the efficacy between early and later rehabilitation intervention. AIM: To investigate the effects of early rehabilitation management of paediatric burnt hands. METHODS: A total of 52 children with burnt hands were allocated into the early intervention group (≤ 1 mo from onset) and a late intervention group (> 1 mo from onset) between January 2016 and December 2017. The children received the same rehabilitation programme including skin care, scar massage, passive ROM exercises, active ROM exercises, compression therapy, orthotic devices wearing and game or music therapy. Rehabilitation assessments were performed before and after the rehabilitation treatment. RESULTS: In the early intervention group, the ROM of the hands was significantly improved after rehabilitation (P = 0.001). But in the late group the effect was not significant statistically (P = 0.142). In the early group, 38.5% of the patients showed significant improvement, while in the late group, 69.2% of the patients showed no significant improvement. The time from onset to posttraumatic rehabilitation (P = 0.0007) and length of hospital stay (P = 0.003) were negatively correlated with the hand function improvement. The length of rehabilitation stay was positively correlated with the hand function improvement (P = 0.005). CONCLUSION: These findings suggest that early rehabilitation might show better results in terms of ROM.
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Neuroprotective effects of dexmedetomidine (Dex) have been reported in various models of brain injury. However, to our knowledge, the neuroprotective mechanism of Dex pretreatment in rats remains unknown. The aim of the present study was to detect the expression of the α2A adrenergic receptor (ADRA2A) in focal ischemic brain tissues and to investigate the protective role and corresponding mechanism of Dex pretreatment in cerebral ischemia in rats. A hypoxia/reoxygenation (H/R) cell model in primary cultured astrocytes and a focal cerebral ischemia/reperfusion (I/R) model in adult rats were used. The expression of ADRA2A and extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the primary cultured astrocytes and rat brain ischemic tissues was detected in the different conditions prior to and following Dex pretreatment using western blotting. The H/R model of primary cultured astrocytes and the focal cerebral I/R model in adult rats were successfully constructed. Under the normal oxygen conditions, 500 ng/ml Dex pretreatment increased the expression of ADRA2A and phosphorylated (p)-ERK1/2 in the astrocytes compared with in the control group. Hypoxic culture for 6 h and then reoxygenation for 24 h decreased the levels of p-ERK1/2 in the astrocytes compared with those in control group. This decrease was prevented by Dex pretreatment for 3 h. The hypoxic culture and then reoxygenation increased the expression of ADRA2A. Similarly, compared with those prior to Dex treatment, the levels of ADRA2A and p-ERK1/2 in the brain ischemic tissues following Dex treatment were increased. The levels of ADRA2A and p-ERK1/2 were 0.72±0.23 and 0.66±0.25 following Dex treatment, compared with 0.76±0.22 and 0.31±0.18, respectively, prior to Dex treatment. The effect of Dex pretreatment increasing p-ERK1/2 expression was attenuated by AG1478 pretreatment. In summary, Dex appeared to promote phosphorylation of ERK1/2 in astrocytes under H/R. As a specific agonist of ADRA2A, Dex may activate phosphorylation of ERK1/2 via ADRA2A in astrocytes. Thus, the neuroprotective role of Dex pretreatment against cerebral ischemic injury may function via ADRA2A-mediated phosphorylation of ERK1/2.
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Targeted therapy can improve the accuracy of diagnosis and treatment in the field of cancer management. Cellular surface engineering can enhance cell functions via mounting functional molecules onto cellular membranes. A novel amphiphilic hyperbranched polymer (AHP) conjugated with oleic acid (OA) and tumor-targeted ligand folic acid (FA) is employed. The lipophilic chain can self-assemble and infuse with the cytomembrane of bone marrow mesenchymal stem cells (BMSCs) with the end of FA left on the outside for targeting. The polymer tailored BMSCs can enhance tumor tropism in gastric cancer. BMSCs are characterized by the low immunogenicity and tumor tropism, which makes them promising targeting carriers. Regarding the integrated advantages of these two vectors, it is demonstrated that the functional amphiphilic AHP-OA-FA enhances the tumor tropism of BMSCs. Flow cytometry, standard MTT assay, and wound-healing assay show that AHP-OA-FA has no influence on CD expression, proliferative capacity, and cell motility of BMSCs, respectively. Furthermore, in vitro transwell assay and ex vivo fluorescence image verify that AHP-OA-FA enhances tumor tropism of BMSCs compared to BMSCs and AHP-OA-Rhodamine B-BMSCs. Finally, histological analysis demonstrates that AHP-OA-FA causes no damage to major organs. The results of this study suggest that living BMSCs self-assembled with a polymer might be a promising vehicle for targeted delivery to cancer cells.
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Células Madre Mesenquimatosas/metabolismo , Polímeros/química , Animales , Células de la Médula Ósea/citología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ácido Fólico/química , Ácido Fólico/farmacología , Humanos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Ratones Desnudos , Neoplasias/metabolismo , Neoplasias/patología , Ácido Oléico/química , Ácido Oléico/farmacología , Imagen Óptica , Ratas , Ratas Sprague-Dawley , Rodaminas/químicaRESUMEN
Two replicase (Rep) proteins, Rep and Rep', are encoded by porcine circovirus (PCV) ORF1; Rep is a full ORF1 transcript, and Rep' is a truncated transcript generated by splicing. These two proteins are crucial for the rolling-circle replication (RCR) of PCV. The N-terminal sequences of Rep and Rep' are identical and interact to form homo- or heterodimers. The three types of dimers perform different functions during replication. A structural examination of the interfacing termini has not been performed. In this study, a crystal structure of dimerized Rep protein N termini was resolved at 2.7 Å. The dimerized protein was maintained by nine intermolecular hydrogen bonds and 15 pairs of hydrophobic interactions. The amino acid residue Ile37 participates in 11 of the hydrophobic interactions, mostly with its side chain. To find the predominant sites for protein dimerization and virus replication, a series of mutant proteins and virus replicons were generated by alanine substitution. Of all the single amino acid substitutions, the mutation at Ile37 showed the greatest effect on protein dimerization and virus replication. A double mutation at Leu35 and Ile37 almost eliminated protein dimerization and had the greatest negative effect on virus replication. These studies demonstrate that Leu35 and Ile37 are the most important residues for protein dimerization and are crucial for virus replication. Our results also show that PCV replication can be decreased by disrupting the dimerization of Rep or Rep' at the N terminus, suggesting that the structural interface responsible for dimerization offers a promising antiviral target.IMPORTANCE Porcine circovirus type 2 (PCV2) is one of the most economically damaging pathogens affecting the swine industry. Although vaccines have been available for more than 10 years, the virus still remains prevalent. More effective strategies for disease prevention are clearly required. The Rep and Rep' proteins of the virus have identical N-terminal regions that interact with each other, allowing the formation of homo- or heterodimers. The heterodimer has crucial functions during different stages of viral replication. Here, we resolved the crystal structure of the Rep (Rep') dimerization domain. The individual residues involved in the intermolecular interaction were visualized in the protein structure, and several interactions were verified by mutant analysis. Our studies show that disrupting the interaction decreases viral replication, thus revealing a new target for the design of antiviral agents.
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Circovirus/enzimología , ADN Helicasas/química , Dimerización , Proteínas Virales/química , Sustitución de Aminoácidos , Animales , Circovirus/química , Cristalización , ADN Helicasas/genética , ADN Helicasas/metabolismo , Replicación del ADN , ADN Viral/genética , Mutación , Porcinos , Proteínas Virales/genética , Proteínas Virales/metabolismo , Replicación ViralRESUMEN
BACKGROUND: In the early stage of severe burn, patients often exhibit a high level of inflammatory mediators in blood and are likely to develop sepsis. High-volume haemofiltration (HVHF) can eliminate these inflammatory mediators. We hypothesised that early application of HVHF may be beneficial in reducing sepsis and improving the prognosis of patients with severe burns. METHODS: Adults patients with burns ≥ 50% total burn surface area (TBSA) and in whom the sum of deep partial and full-thickness burn areas was ≥ 30% were enrolled in this randomised prospective study, and they were divided into control (41 cases) and HVHF (41 cases) groups. Patients in the control group received standard management for major burns, whereas the HVHF group additionally received HVHF treatment (65 ml/kg/h for 3 consecutive days) within 3 days after burn. The incidence of sepsis and mortality, some laboratory data, levels of inflammatory cytokines in the blood, HLA-DR expression on CD14+ peripheral blood monocytes, the proportion of CD25+Foxp3+ in CD4+ T lymphocytes, and the counts of CD3+, CD4+ and CD8+ T lymphocytes were recorded within 28 days post-burn. RESULTS: The incidence of sepsis, septic shock and duration of vasopressor treatment were decreased significantly in the HVHF group. In addition, in the subgroup of patients with burns ≥ 80% TBSA, the 90-day mortality showed significant decreases in the HVHF group. The ratio of arterial oxygen partial pressure to the fraction of inspiration oxygen was improved after HVHF treatment. In the patients who received HVHF treatment, the blood levels of inflammatory cytokines, including tumour necrosis factor-α, interleukin (IL)-1ß, IL-6 and IL-8, as well as the blood level of procalcitonin were found to be lower than in the control group. Moreover, higher HLA-DR expression on CD14+ monocytes and a lower proportion of CD25+Foxp3+ in CD4+ T lymphocytes were observed in the patients in the HVHF group. CONCLUSIONS: Early application of HVHF benefits patients with severe burns, especially for those with a greater burn area (≥ 80% TBSA), decreasing the incidence of sepsis and mortality. This effect may be attributed to its early clearance of inflammatory mediators and the recovery of the patient's immune status. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002616 . Registered on 24 October 2012.
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Quemaduras/complicaciones , Hemofiltración/normas , Sepsis/terapia , Adulto , Quemaduras/mortalidad , Quemaduras/terapia , Citocinas/análisis , Citocinas/sangre , Femenino , Hemofiltración/métodos , Humanos , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Polipéptido alfa Relacionado con Calcitonina/análisis , Polipéptido alfa Relacionado con Calcitonina/sangre , Pronóstico , Estudios Prospectivos , Prevención Secundaria/métodos , Prevención Secundaria/normas , Sepsis/etiología , Sepsis/mortalidad , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
BACKGROUND: We analyzed the relationship of -794 CATT5-8 MIF polymorphisms with soluble MIF in Coronary Atherosclerotic Disease (CAD) patients. METHODS: A total of 256 patients selected, on which 186 normal-coronary and 70 Coronary artery disease subjects, were recruited in the study (Retrospectively registered). Genotyping of -794 CATT5-8 polymorphisms were performed by PCR and DNA sequencing. Serum MIF levels were measured using an ELISA kit. Patients were classified by coronary angiogram, and CAD based on Gensini's integral degree (angiographic scoring system). RESULTS: The allele frequency and genotype frequency of -794 CATT5-8 did not show any differences in normal-coronary subjects and CAD subjects. In CAD patients, serum MIF levels was lower in CATT (5) subjects than in CATT (7) subjects, while the genotype of -794 CATT5-8 did not show differences in serum MIF levels. In addition, we found a decrease in serum MIF levels in carriers of the (5/5) genotypes the -794 CATT5-8 MIF polymorphisms, although it was not significant. There was no relationship of CAD class and the allele frequency of -794 CATT5-8. CONCLUSIONS: This study found no association between CAD class and -794 CATT5-8 MIF polymorphisms with soluble MIF levels in CAD Subjects. TRIAL REGISTRATION: NCT01750502 (November 2012, Retrospectively registered).
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Enfermedad de la Arteria Coronaria/genética , Estenosis Coronaria/genética , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/sangre , Estenosis Coronaria/diagnóstico por imagen , Ensayo de Inmunoadsorción Enzimática , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Oxidorreductasas Intramoleculares/sangre , Factores Inhibidores de la Migración de Macrófagos/sangre , Fenotipo , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: In recent years, a substantial amount of experimental studies have demonstrated that exogenous administration of corticosterone causes anxiety and depressive-like behaviour in rodents which involves hypothalamic-pituitary-adrenal axis dysregulation. Our present study aimed to explore the neuroprotective potential of mangiferin against corticosterone-induced anxiety and depressive-like behaviour. METHODS: Corticosterone (40 mg/kg; subcutaneously) was administered once daily in swiss albino mice for 21 days. Mice were treated simultaneously with mangiferin (40 mg/kg; p.o.), 30 min prior to the corticosterone injection. RESULTS: Chronic administration of corticosterone caused anxiety and depressive-like behaviour in mice which was significantly alleviated by mangiferin treatment. Biochemical analysis revealed that mangiferin treatment significantly attenuated corticosterone-induced oxido-nitrosative stress and neuroinflammation in the hippocampus region. Furthermore, concomitant treatment with mangiferin significantly enhanced the hippocampal brain-derived neurotrophic factor (BDNF) level and decreased the serum corticosterone level in the corticosterone-treated animals. Western blotting analysis revealed that corticosterone administration significantly up-regulated the indoleamine 2,3-dioxygenase (IDO) protein expression level in the hippocampus which was significantly reduced by mangiferin treatment. CONCLUSION: Taken together, our results suggest that mangiferin exerts anti-anxiety and antidepressant effect in corticosterone-treated rats, which is probably mediated through up-regulation of BDNF level along with inhibition of oxido-nitrosative stress, neuroinflammation and IDO up-regulation in the hippocampus region.
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Hipocampo/efectos de los fármacos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Estrés Nitrosativo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Xantonas/farmacología , Animales , Antiinflamatorios/toxicidad , Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Corticosterona/toxicidad , Depresión/inducido químicamente , Regulación hacia Abajo , Masculino , RatonesRESUMEN
BACKGROUND: Hypertrophic scar is one of the most common complications and often causes the disfigurement or deformity in burn or trauma patients. Therapeutic methods on hypertrophic scar treatment have limitations due to the poor understanding of mechanisms of hypertrophic scar formation. To throw light on the molecular mechanism of hypertrophic scar formation will definitely improve the outcome of the treatment. This study aimed to illustrate the negative role of eukaryotic initiation factor 6 (eIF6) in the process of human hypertrophic scar formation, and provide a possible indicator of hypertrophic scar treatment and a potential target molecule for hypertrophic scar. METHODS: In the present study, we investigated the protein expression of eIF6 in the human hypertrophic scar of different periods by immunohistochemistry and Western blot analysis. RESULTS: In the hypertrophic scar tissue, eIF6 expression was significantly decreased and absent in the basal layer of epidermis in the early period, and increased slowly and began to appear in the basal layer of epidermis by the scar formation time. CONCLUSIONS: This study confirmed that eIF6 expression was significantly related to the development of hypertrophic scar, and the eIF6 may be a target molecule for hypertrophic scar control or could be an indicator of the outcomes for other treatment modalities.
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Cicatriz Hipertrófica/metabolismo , Factores de Iniciación de Péptidos/metabolismo , Adulto , Western Blotting , Femenino , Regulación de la Expresión Génica/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
Eukaryotic initiation factor 6 (eIF6) is a pivotal regulator of ribosomal function, participating in translational control. Previously our data suggested that eIF6 acts as a key binding protein of P311 (a hypertrophic scar-related protein; also known as NREP). However, a comprehensive investigation of its functional role and the underlying mechanisms in modulation of myofibroblast (a key effector of hypertrophic scar formation) differentiation remains unclear. Here, we identified that eIF6 is a novel regulator of transforming growth factor-ß1 (TGF-ß1) expression at transcription level, which plays a key role in myofibroblast differentiation. Mechanistically, this effect is associated with eIF6 altering the occupancy of the TGF-ß1 promoter by H2A.Z (Swiss-Prot P0C0S6) and Sp1. Accordingly, modulation of eIF6 expression in myofibroblasts signiï¬cantly affects their differentiation via the TGF-ß/Smad signaling pathway, which was verified in vivo by the observation that heterozygote eIF6(+/-) mice exhibited enhanced TGF-ß1 production coupled with increased α-smooth muscle actin (α-SMA)(+) myofibroblasts after skin injury. Overall, our data reveal a novel transcriptional regulatory mechanism of eIF6 that acts on facilitating Sp1 recruitment to TGF-ß1 promoter via H2A.Z depletion and thus results in increased TGF-ß1 transcription, which contributes to myofibroblast differentiation.
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Diferenciación Celular/genética , Miofibroblastos/citología , Miofibroblastos/metabolismo , Factores de Iniciación de Péptidos/metabolismo , Factor de Transcripción Sp1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Ratones , Ratones Mutantes , Factores de Iniciación de Péptidos/genética , Transducción de Señal/genética , Transducción de Señal/fisiología , Factor de Transcripción Sp1/genéticaRESUMEN
Endomorphin-2 (EM2) and Substance P (SP) exert suppressive and facilitative influences upon nociception, respectively. Although EM2 and SP were often co-expressed in single neurons in dorsal root ganglion (DRG), it is still unknown if and how the nociception-suppressive influences of EM2 might be exerted upon nociception-facilitative effects of SP in the DRG neurons. We examined these issues in the inflammatory pain model rats produced by subcutaneous injection of the complete Freund's adjuvant into the hind paw. The paw withdrawal threshold for mechanical allodynia was measured. Changes of EM2 and SP release were estimated by measuring intrathecal levels of EM2 and SP through in vivo microdialysis analysis of cerebrospinal fluid. The mechanical allodynia was dose-dependently attenuated by intrathecal injection of EM2 or a neurokinin-1 receptor antagonist, and facilitated by intrathecal injection of SP or a mu-opioid receptor (MOR) antagonist. Importantly, intrathecal level of SP was found to be lowered by intrathecal injection of EM2. Morphologically, colocalization of EM2-, MOR- and SP-immunoreactivity in single DRG neurons was observed by immunofluorescent histochemistry, and co-expression of EM2 and SP in large, dense-cored presynaptic vesicles in primary afferents, as well as localization of MOR on pre- and postsynaptic membrane in spinal dorsal horn, was also confirmed electron miscroscopically. Thus, the results indicated that analgesic influences of EM2 upon inflammatory pain might be exerted through suppression of SP release, supporting the assumptions that binding of EM2 to presynaptic MOR might induce such effects.
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Artritis Experimental/fisiopatología , Dolor Crónico/fisiopatología , Hiperalgesia/fisiopatología , Nocicepción/fisiología , Oligopéptidos/fisiología , Receptores Presinapticos/efectos de los fármacos , Médula Espinal/fisiopatología , Sustancia P/metabolismo , Animales , Dolor Crónico/líquido cefalorraquídeo , Dolor Crónico/etiología , Ganglios Espinales/fisiopatología , Hiperalgesia/líquido cefalorraquídeo , Hiperalgesia/etiología , Inyecciones Espinales , Masculino , Microdiálisis , Microscopía Electrónica , Antagonistas del Receptor de Neuroquinina-1/administración & dosificación , Antagonistas del Receptor de Neuroquinina-1/farmacología , Neuronas Aferentes/fisiología , Oligopéptidos/administración & dosificación , Oligopéptidos/líquido cefalorraquídeo , Oligopéptidos/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Opioides mu/antagonistas & inhibidores , Receptores Opioides mu/fisiología , Receptores Presinapticos/fisiología , Médula Espinal/ultraestructura , Asta Dorsal de la Médula Espinal/fisiopatología , Estrés Mecánico , Sustancia P/líquido cefalorraquídeo , Triptófano/administración & dosificación , Triptófano/análogos & derivados , Triptófano/farmacologíaRESUMEN
The objective of this study was to evaluate the efficacy and safety of a traditional Chinese medicine, Fufang Xuelian Burn Ointment (FXBO), to treat superficial and deep second-degree burn wounds. A four-center, randomized, controlled, and prospective study was conducted. Overall, 240 patients with either superficial or deep second-degree burn wounds were enrolled consecutively in this study. Patients who were randomly assigned to the control group (superficial: 72, deep: 48) underwent common burn wound therapy, whereas those randomized to the treatment group (superficial: 72, deep: 48) received common burn wound therapy plus topical FXBO. The healing rate, healing time, effective rate, and safety data were compared between the two groups. The baseline characteristics were comparable for the two groups. The healing rate was 94.79(±7.50) in the control group and 98.60(±5.69) in the FXBO group after 14 days for patients with superficial second-degree burn wounds (P = 0.000), and 95.17(±9.68) versus 97.44(±9.81) at 28 for deep second-degree burn wounds (P = 0.025). The median healing time in the FXBO group were 9 and 21 days for superficial and deep second-degree burns, respectively, compared to 10.5 and 22.5 days, respectively, in control group (P(superficial) = 0.000 and P(deep) = 0.009). The results of the effective rate showed that comprehensive efficacy of the FXBO group was improved compared to the control group for either superficial or deep second-degree burns (P(superficial) = 0.035 and P deep = 0.003). There were no reported drug-related adverse events in both groups. Therefore, FXBO was well tolerated and more effective than control group for treating superficial and deep second-degree burn wounds.
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Quemaduras/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Adolescente , Adulto , Anciano , Quemaduras/fisiopatología , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pomadas , Estudios Prospectivos , Seguridad , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacos , Adulto JovenRESUMEN
Based on the result of randomized controlled trials and meta-analysis recently, the infusion of hydroxyethyl starch (HES) was not shown to over match routine crystalline solution in exerting resuscitation effect against hypovolemia of patients with burn shock, severe systematic infection, or other critical conditions, on the other hand, it may induce renal toxicity and other toxic and side effects. Since the pathological mechanism underlying hypovolemia during shock phase after burn is similar to that of severe systemic infection, we propose to suspend the use of HES for fluid resuscitation during the shock phase of severe burn until further elucidation.
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Quemaduras/terapia , Fluidoterapia , Derivados de Hidroxietil Almidón , Hipovolemia/prevención & control , Choque/terapia , Contraindicaciones , Humanos , ResucitaciónRESUMEN
OBJECTIVE: To evaluate the effect of FLAMIGEL (hydrogel dressing) on the repair of residual burn wound. METHODS: Sixty burn patients with residual wounds hospitalized in 6 burn units from November 2011 to May 2012 were enrolled in the multi-center, randomized, and self-control clinical trial. Two residual wounds of each patient were divided into groups T (treated with FLAMIGEL) and C (treated with iodophor gauze) according to the random number table. On post treatment day (PTD) 7 and 14, wound healing rate was calculated, with the number of completely healed wound counted. The degree of pain patient felt during dressing change was evaluated using the visual analogue scale (VAS). The mean numbers of wounds with score equal to zero, more than zero and less than or equal to 3, more than 3 and less than or equal to 6, more than 6 and less than or equal to 10 were recorded respectively. Wound secretion or exudate samples were collected for bacterial culture, and the side effect was observed. Data were processed with repeated measure analysis of variance, t test, chi-square test, and nonparametric rank sum test. RESULTS: Wound healing rate of groups T, C on PTD 7 was respectively (67 ± 24)%, (45 ± 25)%, and it was respectively (92 ± 16)%, (72 ± 23)% on PTD 14. There was statistically significant difference in wound healing rate on PTD 7, 14 between group T and group C (F = 32.388, P < 0.01). Ten wounds in group T and four wounds in group C were healed completely on PTD 7, with no significant difference between them (χ(2) = 0, P > 0.05). Forty-two wounds in group T and seven wounds in group C healed completely on PTD 14, with statistically significant difference between them (χ(2) = 42.254, P < 0.01). Patients in group T felt mild pain during dressing change for 37 wounds, with VAS score higher than zero and lower than or equal to 3. Evident pain was observed in patients of group C during dressing change for 43 wounds, and it scored higher than 3 and less than or equal to 6 by VAS evaluation. There was statistically significant difference in mean number of wounds with different grade of VAS score between group T and group C (Z = -4.638, P < 0.01). Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Baumanii, and Staphylococcus epidermidis were all detected in both groups, but there was no statistical difference between group T and group C (χ(2) = 0.051, P > 0.05). No side effect was observed in either of the two groups during the whole trial. CONCLUSIONS: FLAMIGEL can accelerate the healing of residual burn wounds and obviously relieve painful sensation during dressing change.
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Vendajes , Quemaduras/terapia , Hidrogeles , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To retrospectively analyze the effect of restrictive fluid management strategy (RFMS) on the early pulmonary function and the prognosis of patients with extremely severe and extensive burn. METHODS: Thirteen patients with extremely severe burn hospitalized from June 2010 to November 2011, being treated with RFMS in the fluid reabsorption stage, were enrolled as treatment group. Twenty-six patients with extremely severe burn hospitalized from March 2008 to November 2011, being treated with normal fluid therapy in the fluid reabsorption stage, were enrolled as control group. The match proportion between treatment group and control group was 1:2. Fluid intake, fluid output, fluid balance (the difference between fluid intake and output), and plasma albumin level from post burn day (PBD) 3 to 10, pulmonary oxygenation index on PBD 3, 5, 7, 10, and 14, occurrence of lung and blood stream infections from PBD 7 to 14, and occurrence of acute respiratory distress syndrome (ARDS), occurrence of other organ complications, and mortality within 2 weeks post burn (PBW) were recorded and compared. Measurement data were processed with t test and randomized blocks analysis of variance, enumeration data were processed with Fisher's exact test. RESULTS: Daily fluid intake of patients showed a tendency of decrease in both groups from PBD 3 to 10. Except for that of PBD 4, there was no statistically significant difference between two groups in fluid intake (with F values from 0.072 to 1.939, P values all above 0.05). Daily fluid output of patients showed a tendency of increase in both groups from PBD 3 to 10. It peaked on PBD 10 in control group and PBD 6 in treatment group. The mean daily fluid output was higher in treatment group than in control group from PBD 4 to 9, but without statistically significant difference (with F values from 0.001 to 3.026, P values all above 0.05). Fluid balance lowered in both groups, and it was the lowest on PBD 10 in control group and PBD 6 in treatment group. Fluid balance was lower in treatment group than in control group from PBD 3 to 7, and it showed statistically significant differences on PBD 4, 5, and 6 (with F values from 4.799 to 8.031, P values below 0.05). Plasma albumin level was higher in treatment group than in control group from PBD 3 to 10, with statistically significant differences observed on PBD 4, 9, and 10 (with F values from 5.691 to 10.551, P < 0.05 or P < 0.01). Pulmonary oxygenation index was higher in treatment group than in control group from PBD 3 to 14, with statistically significant differences observed on PBD 7 (respectively 372 ± 78 in treatment group and 291 ± 92 in control group, F = 5.184, P < 0.05) and 14 (respectively 354 ± 39 in treatment group and 283 ± 72 in control group, F = 8.683, P < 0.05). Lung infection and blood stream infection were respectively observed in 1 and 4 patient (s) in treatment group, and 9 and 11 patients in control group from PBD 7 to 14. Occurrence of ARDS, occurrence of other organ complications, and mortality were fewer in treatment group than in control group within PBW 2, though the differences were not statistically significant (P values all above 0.05). CONCLUSIONS: RFMS is a useful strategy in improving early pulmonary oxygenation of patients with extremely severe and extensive burn by promoting the process of fluid reabsorption and rebalance. This strategy may be also beneficial for the prevention of organ complications as well as a better prognosis in severely burned patients.
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Quemaduras/fisiopatología , Quemaduras/terapia , Fluidoterapia/métodos , Adolescente , Adulto , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Equilibrio Hidroelectrolítico , Adulto JovenRESUMEN
OBJECTIVE: To study effects of P311 on the migration of epidermal stem cells (ESCs) in mice with superficial partial-thickness burn and injured cell model in vitro and to explore the mechanism. METHODS: (1) Eighteen male C(57) BL/6 mice were used. Fifteen of them were inflicted with superficial partial-thickness burn on the back. In three injured mice wound tissue and skin of wound edge were obtained at post burn hour (PBH) 6, 12, 24, 48, 72 respectively. The rest three mice were used as normal control, and samples were harvested with the same method as above. The expressions of P311 in harvested samples were assessed with biotin-streptavidin-peroxidase (SP) staining. (2) Six newly born C(57) BL/6 mice were intraperitoneally injected with 50 µg/g BrdU (two times a day) for three days for ESCs-labelling. Seven weeks later, the mice were inflicted with superficial partial-thickness burn on the back. Serial slices of burn wound tissue were prepared at PBH 72 and immunohistochemically stained with SP for observation of the co-localization of BrdU-positive ESCs and P311-positive cells. (3) The empty vector pAdEasy-enhanced green fluorescence protein (EGFP) and the adenovirus P311-expressing vector named pAdEasy-EGFP-P311 were constructed and packed. Human ESCs were isolated by the method of rapid adhesion to collagen IV. After being divided into P311 high-expressing group (n = 3) and EGFP control group (n = 3), the ESCs in two groups were respectively infected by pAdEasy-EGFP-P311 and pAdEasy-EGFP. Scratching assay was performed on ESCs in both groups after they were treated by mitomycin C for 2 hours. The remaining area within the fixed range was measured at post scratching hour (PSH) 0, 24, 48, and 72, and the wound-area healing rate was calculated. Data were processed with independent samples t test. RESULTS: (1) Expression amount of P311 was different in different parts of wound at different time points after burn. Expression amount of P311 in the newly formed epidermis and hair follicle of wound increased along with prolongation of time. Expression amount of P311 in the epidermis and hair follicle of wound edge peaked at PBH 12 and then decreased to normal levels at PBH 72. (2) Co-localization of BrdU-positive ESCs and P311-positive cells was observed in the new epidermal layer of wound tissue of mice, where ESCs were labeled by BrdU. (3) At PSH 48 and 72, wound-area healing rate was obviously higher in P311 high-expressing group [(69 ± 31)%, (89 ± 26)%] than in EGFP control group [(35 ± 12)%, (46 ± 31)%, with t values respectively -2.336, -2.611, P values all below 0.05]. CONCLUSIONS: P311 may promote the migration of ESCs both in rats with superficial partial-thickness burns and in injured cell model in vitro, and it may play an important role in wound healing.
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Quemaduras/metabolismo , Células Epiteliales/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas Oncogénicas/metabolismo , Animales , Animales Recién Nacidos , Movimiento Celular , Células Cultivadas , Modelos Animales de Enfermedad , Células Epidérmicas , Epidermis/lesiones , Células Epiteliales/citología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Células Madre/citología , Cicatrización de HeridasRESUMEN
OBJECTIVE: To observe the effect of nitric oxide (NO) on adhesion, proliferation, and migration of human epidermal stem cells (ESC) in vitro. METHODS: ESC were isolated and cultured by the modified method of rapid attachment to type IV collagen. (1) Morphology of cells was observed under inverted phase-contrast microscope. Expression levels of integrin ß(1) and cytokeratin 19 (CK19) of cells were determined by Western blotting and immunofluorescence staining. (2) After being treated with scratching, ESC adhered to the wall was respectively treated with nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) in the concentration of 1, 10, 100, 500 µmol/L. ESC without treatment of SNAP was used as control. The migration rate of ESC was detected at post scratching hour (PSH) 12 and 24. The chemotaxis of ESC (treated with SNAP in above-mentioned concentration) was tested by Transwell assay, and the transferred cell number was counted. (3) ESC was respectively treated with SNAP in the concentration of 10, 100, 500 µmol/L for 1 h. ESC without treatment of SNAP was used as control. The adhesion of ESC was detected with adhesion test, and the inhibition rate of adhesion was calculated. The proliferation of ESC (denoted as absorbance value) was determined by microplate reader at post-treatment hour (PTH) 0, 12, 24, 48. Data were processed with one-way analysis of variance and Dunnett t test. RESULTS: (1) Small clone formed on post culture days (PCD) 5 to 9. On PCD 10 to 14, cell proliferation sped up. CK19 and integrin ß(1) were detected to be expressed in the isolated cells. The cells were identified as ESC. (2) Compared with that of ESC without treatment of SNAP [(35.7 ± 0.3)%, (45.7 ± 5.0)%], migration of ESC treated with SNAP in the concentration from 1 to 100 µmol/L was promoted at PSH 12 and 24. Migration rates of ESC treated with 100 µmol/L SNAP were the highest [respectively (48.8 ± 2.7)%, (82.1 ± 15.8)%, with t value respectively 8.34, 5.10, P values both below 0.01]. The number of ESC transferred to membrane after being treated with 100 µmol/L SNAP was significantly larger than that of ESC without treatment of SNAP (t = 9.24, P = 0.00). (3) Absorbance values of ESC treated with 100, 500 µmol/L SNAP were obviously higher than that of ESC without treatment of SNAP (with t value respectively 4.30, 4.67, P values both equal to 0.00). Proliferation of ESC treated with 100, 500 µmol/L SNAP was obviously stronger than that of cells without treatment of SNAP at PTH 24, 48 (with t values from 2.84 to 8.17, P values all below 0.05). CONCLUSIONS: Exogenous NO in suitable concentration can promote the migration of human ESC. Exogenous NO can inhibit the adhesion and promote the proliferation of human ESC in vitro.
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Células Epiteliales/citología , Óxido Nítrico/farmacología , Células Madre/citología , Movimiento Celular/efectos de los fármacos , Proliferación Celular , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Humanos , Células Madre/efectos de los fármacosRESUMEN
It is essential for the development of modern clinical medicine to establish a professional facility and team for wound healing. There is some successful experience of constructing and running the wound healing center to be mirrored at home and abroad. The construction of the facility and team for wound healing will be promoted by guideline issuing, profession certification, and others, which would push forward the clinical treatment and basic research of wound healing.